(Hypertension. 1999;33:408-413.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Afferent Arteriolar Vasodilation to the Sulfonimide Analog of 11,12-Epoxyeicosatrienoic Acid Involves Protein Kinase A
From the Department of Physiology, Tulane University School of Medicine, New Orleans, La (J.D.I., E.W.I., P.C.D.); and the Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Tex (K.M.R., J.R.F.).
Correspondence to John D. Imig, PhD, Department of Physiology, SL39, Tulane University School of Medicine, 1430 Tulane Ave, New Orleans, LA 70112. E-mail jdimig{at}mailhost.tcs.tulane.edu
Abstract—The current study determined the contribution of protein kinase-A (PKA) and protein kinase-G (PKG) to the vasodilation elicited by the N-methylsulfonimide analog of 11,12-epoxyeicosatrienoic acid (11,12-EET). Experiments were performed, in vitro, using the juxtamedullary nephron preparation combined with videomicroscopy. The response of afferent arterioles to the sulfonimide analog of 11,12-EET, was determined before and after inhibition of PKA, PKG, or guanylyl cyclase. Afferent arterioles, preconstricted with 0.5 µmol/L norepinephrine, averaged 18±1 µm (n=25) at a renal perfusion pressure of 100 mm Hg. Superfusion with 0.01 to 100 nmol/L of the 11,12-EET analog caused a graded increase in diameter of the afferent arteriole. Vessel diameter increased by 11±1% and 15±1%, respectively, in response to 10 and 100 nmol/L of the 11,12-EET analog. The afferent arteriolar response to 10 and 100 nmol/L of the 11,12-EET analog was significantly attenuated during inhibition of PKA with 10 µmol/L H-89 (n=7) or 5 µmol/L myristolated PKI (n=6), such that afferent arteriolar diameter increased by only 5±2% and 2±1%, respectively, in response to 100 nmol/L of the 11,12-EET analog. In contrast, the afferent arteriolar vasodilatory response to the 11,12-EET analog was unaffected by PKG or guanylyl cyclase inhibition. In the presence of 200 µmol/L histone H2B (n=5) or 10 µmol/L ODQ (n=7), the afferent arteriolar diameter increased by 16±3% and 12±2%, respectively, in response to 100 nmol/L of the 11,12-EET analog. These results demonstrate that activation of PKA is an important mechanism responsible for the afferent arteriolar vasodilation elicited by the sulfonimide analog of 11,12-EET.
Key Words: metabolites, cytochrome P450 • kidney • endothelium-derived hyperpolarizing factor • arterioles • cyclic adenosine monophosphate • cyclic guanosine monophosphate
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